An orally bioavailable fluoro-diaminopyrimidine compound that acts as a potent, reversible and ATP-competitive inhibitor of LRRK2 activity (IC50=4.76 and 6.87nM for hr-wt-LRRK2 and G2019S-LRRK2 mutant, respectively) with selectivity over PLK4, GAK, TNK1, CAMKK2, and PIP4K2C (IC50 <300nM) in a 185-kinase panel. Does neither exert cytotoxicity nor block neuronal development of human or rat cortical neurons at 1uM. Shown to prevent GS-LRRK2-induced neuronal injury (EC50 ~4nM) and G2019S- or R1441C-LRRK2-mediated neuronal death in both rat and human cortical neurons (EC50 ~100nM). Even though exhibits favorable pharmacokinetic profile and metabolic stability, and yet suffers from limited blood brain barrier penetration (~4%).
Formula:C22H25FN6O4S · HCl
Molecular Weight:525.0
Solubility:DMSO (5mg/ml) or H2O (1mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
